We have recently observed that certain rheumatic fever (RF) associated strains of group A streptococcus adhere more avidly in vitro to pharyngeal cells from persons with rheumatic fever or rheumatic heart disease than to pharyngeal cells from normal persons. These studies are investigating the nature of the streptococcal-pharyngeal cell interaction. We are comparing routine group A streptococcal isolates with low pharyngeal adherence to high adhering RF associated isolates regarding: 1. susceptibility of adherence to inhibition by lipoteichoic acid, 2. the dependence of adherence on the growth phase and concentration of the bacteria, 3. the effect on bacterial adherence of incubation temperature, pH, and duration of incubation, and 4. capsular size. We have examined the biochemical characteristics of the pharyngeal cell site to which streptococci adhere using enzymes to either uncover or destroy the adherence site, and using various chemical compounds in the reaction mixture to attempt to inhibit adherence. This site has been identified as being protein containing since trypsin inhibits attachment. Future studies will use several techniques to attempt to create an antisera specific for the epithelial cell reactive site. An improved understanding of the streptococcal-epithelial cell interaction could increase our knowledge regarding the etiology of rheumatic fever, and could allow better identification of rheumatogenic streptococcal strains and of individuals who are susceptible to rheumatic fever.